3. Acids and Bases

Would the following reactions go to the right or the left? Draw the products and label ALL species. Provide the full mechanism.

Would the following reactions go to the right or the left? Draw the products and label ALL species. Provide the full mechanism.

Would the following reactions go to the right or the left? Draw the products and label ALL species. Provide the full mechanism.

Would the following reactions go to the right or the left? Draw the products and label ALL species. Provide the full mechanism.

Which anion in each pair would you expect to react more quickly with H⁺ ?

(b) <IMAGE>

If reacted with a strong base, which of the labeled protons would you expect to be removed first?

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In each pair, choose the most acidic compound. Justify your answer. The most acidic proton in each compound has been indicated.

(b) <IMAGE>

Rationalize the difference in pKₐ values for the two hydroxyl groups.

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p-Nitrophenol (pKₐ = 7.2) is ten times more acidic than m-nitrophenol (pKₐ = 8.4) Explain. [This concept is the subject of Section 24.2.1 in the chapter on benzene.]

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Which is the most stable base in each pair?

(a) <IMAGE>

Which is the most acidic compound in each pair?

(b) <IMAGE>

Which is the most acidic compound in each pair?

(c) <IMAGE>

Using qualitative reasoning for the acid–base reactions shown,

(i) which is stronger, the base or the conjugate base?

(ii) Which side of the reaction is favored?

(iii) Would you expect a greater than or less than 1?

(c) <IMAGE>

Rank the following alcohols in order of descending pKₐ value. Explain your ranking.

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Which of the following indicated atoms would you expect to be most basic?

(b) <IMAGE> vs. <IMAGE>

The nitrogen screened in purple in Figure 4.43 is not protonated at physiological pH. Why?

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Which is the most stable base in each pair?

(b) <IMAGE>

(••) Identify the stronger base in each pair. Explain your choice. Citing pKₐ values is not an acceptable answer.

(d) <IMAGE>

Imidazole is a heteroaromatic base. Which nitrogen, a or b, is most basic?

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Without using pKₐ values, pick out the least reactive (most stable) base in each pair. Explain your answer.

(b) <IMAGE>

Using qualitative reasoning for the acid–base reactions shown, 

(i) which is stronger, the acid or the conjugate acid? 

(ii) Which side of the reaction is favored? 

(iii) Would you expect a greater than, equal to, or less than 1?

(b) <IMAGE>

Identify the most stable conjugate base in each pair. Tell which structural features you analyzed and why you weighted them as you did in picking one answer.

(a) <IMAGE>

Identify the most stable conjugate base in each pair. Tell which structural features you analyzed and why you weighted them as you did in picking one answer.

(f)

Identify the most acidic proton in each pair. Tell which structural features you analyzed and why you weighted them as you did in picking one answer. [Always start by drawing the conjugate base.]

(b) <IMAGE>

Identify the most acidic proton in each pair. Tell which structural features you analyzed and why you weighted them as you did in picking one answer. [Always start by drawing the conjugate base.]

(d) <IMAGE>

Which acid in each pair would you expect to more readily donate a proton to a basic compound?

(a) <IMAGE>

Why is the value of protonated hydroxylamine (6.0) so much lower than the value of a protonated primary amine such as protonated methylamine (10.7)?

(••) In light of your answers to Assessments 24.54 and 24.55, rank the following based on the rate of protonation of the alkene (1 = most basic, 6 = least basic). [Ignore the fact that the alkene may not be the most basic site in the molecule.]

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(•••) Consider the following drugs used to treat the indicated diseases. Would you expect the activity of these drugs to be impacted by a patient taking other medicines for acid reflux disease?

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Which is the most stable base in each pair?

(c) <IMAGE>

Explain why a base can remove a proton from the a-carbon of N,N-dimethylethanamide but not from the

a-carbon of either N-methylethanamide or ethanamide.

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Citrus fruits are rich in citric acid, a compound with three COOH groups. Explain the following:

a. The first pKa (for the COOH group in the center of the molecule) is lower than the pKa of acetic acid.

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Which of the following amino acid side chains can help remove a proton from the a-carbon of an aldehyde?

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Rank the following compounds from easiest to hardest at removing a proton from its methyl substituent:

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CCl3CH2OH CH2ClCH2OH CHCl2CH2OH

Ka=5.75×10−13 Ka=1.29×10−13 Ka=4.90×10−13

b. Explain the relative acidities.

Glycine has pKa values of 2.3 and 9.6. Do you expect the pKa values of glycylglycine to be higher or lower than these values?

Fosamax (shown on the previous page) <IMAGE> has six acidic groups. The active form of the drug, which has lost two of its acidic protons, is shown in the box. 

(Notice that the phosphorus atom in Fosamax and the sulfur atom in [Problem 36] <IMAGE> can be surrounded by more than eight electrons because P and S are below the second row of the periodic table.)

a. Why are the OH groups bonded to phosphorus the strongest acids of the six groups?

b. Which of the remaining four groups is the weakest acid?

e. Which has a greater Ka: cyclohexylammmonium ion or anilinium ion?

f. Which is a stronger acid: cyclohexylamine or aniline?

The pKa values of a few ortho-, meta-, and para-substituted benzoic acids are shown below:

<IMAGEs>

The relative pKa values depend on the substituent. For chloro-substituted benzoic acids, the ortho isomer is the most acidic and the para isomer is the least acidic; for nitro-substituted benzoic acids, the ortho isomer is the most acidic and the meta isomer is the least acidic; and for amino-substituted benzoic acids, the meta isomer is the most acidic and the ortho isomer is the least acidic. Explain these relative acidities.

NH2: meta > para > ortho

b. Explain why, when the guanidino group of arginine is protonated, the double-bonded nitrogen is the nitrogen that accepts the proton.

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Which compound is the strongest base?

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Consider the following compounds that vary from nearly nonacidic to strongly acidic.

Draw the conjugate bases of these compounds, and explain why the acidity increases so dramatically with substitution by nitro groups.

CH4 pKa= 50

CH3NO2 pKa= 10.2

CH2(NO2)2 pKa= 3.6

CH(NO2)3 pKa= 0.17

Choose the more acidic member of each pair of isomers, and show why the acid you chose is more acidic.

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Choose the more acidic member of each pair of isomers, and show why the acid you chose is more acidic.

f. <IMAGE> or <IMAGE>

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The pKa of ascorbic acid (vitamin C, page 55) <IMAGE> is 4.17, showing that it is slightly more acidic than acetic acid (CH3COOH, pKa 4.74).

a. Show the four different conjugate bases that would be formed by deprotonation of the four different OH groups in ascorbic acid.

b. Compare the stabilities of these four conjugate bases, and predict which OH group of ascorbic acid is the most acidic.

Choose the more basic member of each pair of isomers, and show why the base you chose is more basic.

c. <IMAGE> or <IMAGE>

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Choose the more basic member of each pair of isomers, and show why the base you chose is more basic.

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The following compounds can all react as bases.

CH3CH2NH2 <IMAGE>

CH3CONH2 <IMAGE>

NaOH

CH3CH2OH <IMAGE>

NaNH2

b. Rank the conjugate acids in the order you would predict, from most stable to least stable.

Four pairs of compounds are shown. In each pair, one of

the compounds reacts more quickly, or with a more favorable

equilibrium constant, than the less conjugated system.

In each case, explain the enhanced reactivity.

(d) <IMAGE>

Use resonance forms of the conjugate bases to explain why methanesulfonic acid (CH₃SO₃H, pKa = - 2.6) is a much stronger acid than acetic acid (CH₃COOH, pKa = 4.8).

Tenormin, a member of the group of drugs known as beta-blockers, is used to treat high blood pressure and improve survival after a heart attack. It works by slowing down the heart to reduce its workload. Which atom in Tenormin is the most basic?

A carboxylic acid ( pKₐ = 5) is 10₁₁ times more acidic than an alcohol. Why? (pKₐ = 16.)

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